Modeling influenza and coinfection
Establishment of novel interventional strategies for influenza (co)infection by experimental analyses and mathematical modeling of infection
Influenza A virus (IAV) - infected hosts are hypersusceptible to secondary bacterial infections with Streptococcus (S.) pneumoniae. While many immunological aspects of IAV/bacterial coinfection have previously been subject of basic research, the underlying mechanisms of coinfection pathogenesis remain poorly understood. The methodology of our current interdisciplinary research project combines mathematical modeling, engineering science and tailored in vivo infection experiments. This project is conducted in close cooperation with scientists from the Frankfurt Institute for Advanced Studies (FIAS). Together we aim at:
- Developing a mathematical model of influenza pathogenesis in order to quantify immunoregulatory mechanisms in the infected host that will ultimately help to predict or prevent severe courses of this infectious disease.
- Implementation of a non-linear observer as an in silico tool for improving and refining viral disease predictions.
- Elucidation of the immunological role of interferon-γ, which is released by natural killer (NK) cells and CD8+ T cells during IAV infection. By inducing the functional impairment of alveolar macrophages this inflammatory cytokine is believed to play a pivotal role in the hypersusceptibility of IAV-hosts to bacterial coinfection with S. pneumoniae.
Altogether, the iterative process of experimental (=wet lab)-based refinements of simulations and mathematical models will aid in hypothesis-finding and –testing, respectively and thereby this research project will ultimately help elucidating the lethal synergism between IAV and S. pneumoniae and pave the way for novel prophylactic and interventional anti-infective strategies.
Dr. Esteban Hernandez-Vargas (Frankfurt Institute for Advanced Studies) (http://www.systemsmedicine.de)
Prof. Birgitta Henriques Normark (Karolinska Institutet, Sweden)